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Biomedical subjects

R Engler

Publications and source records attributed to R Engler.

At least 19 recordsLinked to original sources
PubMed1992

Toxicological considerations for protein components of biological pesticide products.

The toxicity of protein components of microbial pesticide products is evaluated at EPA by requiring that pesticide manufacturers conduct a thorough taxonomic evaluation of the active microbial ingredient. The requirement for acute toxicity testing by dosing laboratory animals with the active microbial ingredient and with fermentation growth medium materials provides additional information on the toxicity of protein components of microbial pesticides. The potential for toxicity from proteins associated with contaminating organisms is addressed by use of appropriate quality control procedures to minimize or prevent growth of contaminants and by screening of fermentation batches for known human/mammalian pathogens. These considerations also would apply to any biochemical pesticide that is formed via the growth of a microorganism. If a protein itself is intended for commercial use as an active pesticide ingredient, acute exposure studies and in vitro digestibility studies could be done to answer potential concerns regarding toxicity.

Animals↗
PubMed1992

Cysteine and glycine supplementation modulate the metabolic response to tumor necrosis factor alpha in rats fed a low protein diet.

Responses to cytokines entail synthesis of substances rich in cysteine and glycine, such as glutathione (GSH), metallothionein and some plasma proteins. To examine the importance of an adequate supply of cysteine and glycine, we fed rats a low protein diet supplemented with L-cysteine and glycine, separately or in combination, or L-alanine, or a high protein diet for 1 wk before injection with tumor necrosis factor alpha (TNF) or saline. The high protein diet-fed group had greater liver weight and zinc and GSH concentrations after TNF than the group fed the low protein diet supplemented with alanine. Glycine and cysteine supplementation resulted in greater liver weight after TNF treatment than did alanine supplementation. Cysteine supplementation had a similar influence on GSH concentration. Ceruloplasmin, alpha-2-macroglobulin and alpha-1-acid glycoprotein were higher in TNF-treated rats than in saline controls in each dietary group. However, feeding supplementary glycine and cysteine and the high protein diet often resulted in different values than seen in animals fed the low protein diet supplemented with alanine. Paradoxically, lower ceruloplasmin concentrations were observed in animals fed the former diets than in those fed the latter. alpha-2-Macroglobulin concentration was lower in all animals fed low protein diets than in those fed the high protein diet. alpha-1-Acid glycoprotein was lowest in groups fed cysteine-supplemented diets and highest in the glycine-supplemented group.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1992

Anti-RNA polymerase I antibodies in the sera of MRL lupus mice at the initial stages of disease are directed primarily against phosphorylation-dependent epitopes.

Anti-RNA polymerase I (RPI) antibodies in the sera of MRL/Mp-lpr/lpr and MRL/Mp(-)+/+ mice, which develop an autoimmune disease similar to human systemic lupus erythematosus, were screened for reactivity with purified RPI or RPI which had been dephosphorylated. In every case (n = 10), dephosphorylation of RPI resulted in a significant decrease (33-95%) in antibody binding. The anti-RPI antibodies in the sera of the same mice approximately 6 weeks later also reacted better with untreated as compared to dephosphorylated RPI but, in every case, the decrease in antibody (0-30%) caused by dephosphorylation was substantially diminished. That the proportion of anti-RPI antibodies in the sera of MRL mice decreased with progression of lupus-like disease was confirmed by closely monitoring the antibodies over the course of disease. Anti-RPI antibodies produced at the earliest stages appeared to be directed almost exclusively against phosphorylation-dependent determinants since dephosphorylation of RPI essentially abolished antibody binding. Subsequently, the percentage of the total anti-RPI antibodies in the sera of these mice directed towards phosphorylation-independent epitopes increased linearly with time. The importance of phosphorylation-dependent epitopes on RPI for the development of the anti-RPI autoimmune response was supported by the observation that treatment of mice with alkaline phosphatase partially attenuated anti-RPI antibody production.

Animals↗
PubMed1991

Proclivity of activated neutrophils to cause postischemic cardiac dysfunction: participation in stunning?

Myocardial stunning is a reversible defect in contractile function provoked by brief episodes of ischemia followed by reperfusion. Many studies have demonstrated the potential involvement of free radicals in the etiology of myocardial stunning. While activated neutrophils have the capacity to release free radicals and evoke contractile dysfunction, it is not clear that this potential is realized in the absence of myocellular damage. Attempts to define the contribution of activated neutrophils to myocardial stunning by removing the cells from the bloodstream are contradictory, and the apparent simplicity of this seemingly logical approach is an illusion. For example, it is not known how many neutrophils are required to induce contractile failure, the site of action within the heart, the mechanisms that may be responsible, or even the time course or process of neutrophil activation. The production of free radicals and endothelial dysfunction may create conditions propitious for neutrophil recruitment. However, because activated neutrophils synthesize and release various mediators that are potentially toxic to myocardium, once the stage is reached for leukocyte accumulation, it may herald the progression from reversible to irreversible cardiac injury.

Animals↗
PubMed1991

The weight of the evidence among group C carcinogens.

Pesticide chemicals (more than 40) with limited evidence for carcinogenicity in animal experiments, and assigned to Group C according to the EPA Guidelines for Carcinogen Risk Assessment, were further analyzed and ranked by refining the weight of the evidence evaluation. For some of these chemicals there were considerable concern with respect to their potential as human carcinogens and for others there was minimal concern. A clear tumor response at several doses, malignancy of the tumors, the tumor type (rare versus common), the timing of the tumor, and the observance of tumors in both sexes raised the concern for potential human carcinogenicity, as did ancillary information such as the structure-activity relationship and genotoxicity. The design and quality of the studies used in the evaluation were significant factors in reaching a conclusion concerning the carcinogenic potential of the chemicals. Potency factors (Q1*) calculated for these chemicals indicated no correlation with the level of biological evidence for carcinogenicity.

Animals↗
PubMed1979

Is immunochemical determination of haptoglobin phenotype dependent?

Immunochemical methods have been used to determine the concentration of haptoglobins. The dependence on the phenotype was tested with highly purified Hp 2-1, Hp 2-2 and Hp 1-1, by immunonephelometry and radial immunodiffusion (RID). Measurements with three different instruments: automated immunonephelometer (AIP, Technicon), laser nephelometer (LN, Behring) and immunochemistry system (ICS, Beckman) were performed. For each type of apparatus antisera against a pool of haptoglobins were provided by the respective manufacturers. Some experiments were done with an antiserum to the haptoglobin heavy chain prepared in the laboratory. This study shows that haptoglobin determination depends neither on the physical geometry of the instruments or on the type of antiserum used in this work. In contrast, the data display a dependence on haptoglobin phenotype. When Hp 2-1, the most common phenotype, is taken as a standard, thd values obtained for Hp 2-2 are in good agreement with those obtained for Hp 2-1. However, the values obtained for Hp 1-1 are overestimated unless they are corrected by an experimental factor which has been determined in this study.

Haptoglobins↗
PubMed1979

Efficacy of a new oral agent (tocainide) in the acute treatment of refractory ventricular arrhythmias.

To assess the efficacy of tocainide, a new oral analog of lidocaine, 30 patients with ventricular arrhythmias refractory to quinidine, procainamide and propranolol were treated with this agent. The dose of tocainide ranged from 400 to 800 mg every 8 hours. Peak tocainide blood levels 1 to 4 hours after administration ranged from 5.0 to 15.0 microgram/ml (mean 10.3). The suppression of ventricular premature beats by 75 percent or more was arbitrarily used as a measure of drug efficacy. In 13 patients who met this criterion, ventricular premature complexes, assessed with 24 hour ambulatory tape monitoring, decreased by an average of 88 percent. In 8 of 11 patients, repeated symptomatic bouts of ventricular tachycardia were completely suppressed. Considering both the response of ventricular premature complexes and the abolition of ventricular tachycardia, 18 patients (60 percent) responded to tocainide. Twenty-one patients (70 percent) had initial gastrointestinal and central nervous system side effects; most of these were transient or responded to a reduction in dose. In two patients disorientation and a skin rash required withdrawal of tocainide. These adverse effects did not appear to be due to the interaction of tocainide with other antiarrhythmic agents. It is concluded that tocainide is an effective oral agent for the therapy of potentially lethal ventricular arrhythmias refractory to other medication.

Administration, Oral↗
PubMed1979

[Preparation and seric form of rabbit C reactive protein].

The preparation of rabbit C-reactive protein (CRP) involves a single step affinity chromatography. This preparation takes advantage of the calcium-dependent affinity of CRP for an agarose gel bearing 2-aminoethanol dihydrogen-phosphate as a ligand. A prior chromatography on agarose gel without the ligand allows the uptake of the serum amyloid P-component (SAP). The CRP prepared according to this method is able to form precipitating complexes in agarose with rabbit lipoproteins. The specificity of these interactions is studied. It is demonstrated that CRP-High Density Lipoproteins (HLD) association produces a second precipitation arc when the pure CRP is revealed by a specific antiserum in agarose. Moreover, CRP in the serum is shown to be in the bound form only, and the binding involves Low Density Lipoproteins (LDL) exclusively.

Animals↗
PubMed1977

Platelet aggregate ratios--standardization of technique and test results in patients with myocardial ischemia and patients with cerebrovascular disease.

The technique for measuring platelet aggregate ratios described by Wu and Hoak (1974) was evaluated in normal subjects. The following had no influence upon the test result: age, sex, fasting versu the postprandial state, and the degree of stasis prior to drawing the sample. Variance within subjects was small compared to variance between subjects (0.009 versus 0.0053, p less than 0.01). Platelet aggregate ratios were then measured in 36 patients with coronary artery disease hospitalized with acute chest pain. Their mean platelet aggregate ratio of 0.86 was identical to the mean ratio for 47 normal subjects. Greater variability was found within patients (between samples) than within the normal subjects. This observation raises doubts about the significance of a single measurement of platelet aggregate ratio in such acutely ill patients. Mean platelet aggregate ratios measured daily did not differ over a 7-day period between 11 patients who developed a myocardial infarction and 10 patients who did not. A normal mean platelet ratio was also found on a single measurement from 30 patients with a history of completed stroke (0.87) and from 11 patients with a history of transient ischemic attacks (0.92).

Adult↗
PubMed1977

[Immunochemical determination of human hemoglobin in biological fluids (author's transl)].

An assay of human hemoglobin by immunonephelometry-electroimmunodiffusion is proposed. Concentrations in the range from 5 to 180 mg% can be determined to within 2--5% accuracy. The immunonephelometric assay is independent of the presence of haptoglobin whereas the electroimmunodiffusion assay is not. This immunochemical assay, independent of the peroxydase activity of hemoglobin, can be carried out in any biological fluid (plasma, urine, gastric fluid).

Evaluation Studies as Topic↗
PubMed1977

Pharmacologic and hemodynamic influences on the rate of isovolumic left ventricular relaxation in the normal conscious dog.

We studied the effects of acute pharmacologic and hemodynamic interventions on isovolumic left ventricular relaxation in 19 conscious dogs using micromanometer tip catheters. Isoproterenol (11 studies) augmented peak rate of rise of left ventricular pressure [(+) dP/dt] by 1,275+/-227 (SE) mm Hg/s (P < 0.001) and dP/dt at an isopressure point of 35 mm Hg during isovolumic relaxation [(-) dP/dt(35)] by 435+/-80 mm Hg/s (P < 0.001). Peak (-) dP/dt decreased by 467+/-89 mm Hg/s (P < 0.002). The time constant, T, derived from the logarithmic fall of pressure during isovolumic relaxation, shortened from 20+/-2.8 to 14.9+/-1.8 ms (P < 0.003). Calcium (11 studies) increased peak (+) dP/dt and (-) dP/dt(35) (both P < 0.0001); peak (-) dP/dt was unchanged. T shortened from 20.4+/-1.8 to 17.3+/-1.5 ms (P < 0.002). Volume (13 studies) did not affect either dP/dt or T. Phenylephrine (13 studies) augmented peak (-) dP/dt, but reduced (-) dP/dt(35) (both P < 0.01); T lengthened from 22.1+/-1.5 to 32.5+/-1.5 ms (P < 0.01). In 15 studies, rapid atrial pacing increased peak (+) dP/dt and (-) dP/dt(35) (both P < 0.01). In the first post-pacing beat, peak (-) dP/dt and (-) dP/dt(35) decreased (both P < 0.01), although peak (+) dP/dt increased further. T paralleled values of (-) dP/dt(35). In five dogs, beta adrenergic blockade had no significant effect on any variable after calcium, volume, or phenylephrine infusion or during or after atrial pacing when the pre-and post-propranolol states were compared. We conclude that positive inotropic interventions augment both left ventricular contraction and relaxation. The changes in isovolumic relaxation are independent of alterations in sympathetic tone produced by beta-adrenergic blockade. Peak (-) dP/dt may not be a valid measure of left ventricular relaxation rate during acute alterations in inotropic state or afterload.

Animals↗
PubMed1977

Immunochemical study on serum proteins in systemic sclerosis.

Forty one patients with systemic sclerosis were studied after separation into three groups according to Barnett's classification. A multi-dimensional statistical analysis eight serum proteins revealed a difference between control patients and patients with type I and type II scleroderma. Type I scleroderma was characterised by a rise in alpha 2 macroglobulin and in the C4 fraction of complement, whilst in type II scleroderma all the proteins studied were raised, with the exception of CO complement, which was normal, and transferrin which was markedly decreased.

Blood Proteins↗